Preclinical Core Abstract The Preclinical Core (PC) provides IDDRC investigators with innovative, advanced approaches to conduct research spanning fine-grained resolution at the molecular and cellular level, to regional neurocircuitry and connectivity across brain, to multi-domain characterization of mouse behavior. In this application, 40 projects from 21 IDDRC investigators are proposed for core access in studies using models of ADHD, Angelman syndrome, ASD, childhood ataxia, epilepsy, intellectual disability, Joubert syndrome, Pitt-Hopkins syndrome, Rett syndrome, and other neurodevelopmental disorders. The PC has three components, the Mouse Behavioral Phenotyping Laboratory, the Neuroscience Microscopy Facility, and the Small Animal Imaging Service, which, together, offer a broad range of resources and expertise for multidisciplinary IDD research. Services include consultation with expert core faculty, an extensive battery of mouse behavioral testing, training in cutting-edge microscopy methods, acquisition and analysis of quantitative MRI data, and access to state-of-the-art laboratory facilities. A critical goal for the Core is to facilitate projects integrating complementary approaches, such as microscopy analysis of cortical architecture and behavioral evaluation of cognitive phenotypes, to enhance understanding of underlying pathophysiology and structure-function relationships in neurodevelopmental disorders. Within the IDDRC, the PC partners with the Clinical Translational Core and Data Science Core around the use of machine-learning approaches and the establishment of automated data-processing pipelines for new methods development. Overall, the PC provides expertise and infrastructure that has become essential for our IDDRC research using preclinical models, with the overarching aim of supporting breakthrough, transformative science in diagnosis, prevention, and treatment of developmental disorders. 1